into glistening cellular spheres in the incubator. Using the technique that he had perfected on monkeys—the peeling away of the outer layers, the gentle coaxing of cell growth on “feeders” and nurse cells—Thomson isolated a few human embryonic stem cells. Implanted into mice, these cells were capable of generating all three layers of the human embryo—the primordial sources of all tissues, such as skin, bones, muscles, nerves, intestines, and blood.
The stem cells that Thomson had derived from IVF-discarded embryos recapitulated many features of human embryogenesis, but they still had a major limitation: although they were capable of making virtually all human tissues, they would not efficiently generate some tissues, such as sperm and egg cells. A genetic change introduced into these ES cells could thus be transmitted into all cells of the embryo—except to the most important ones: the cells capable of transmitting the gene to the next generation. In 1998, soon after Thomson’s paper had been published in Science, groups of scientists around the world, including researchers from the United States, China, Japan, India, and Israel, began to derive dozens of embryonic stem cell lines from fetal embryonic tissues in the hopes of discovering a human ES cell capable of germ-line transmission of genes.
But then, with little warning, the field was frozen shut. In 2001, three years after Thomson’s paper, President George W. Bush sharply restricted all federal ES cell research to the seventy-four cell lines that had already been created. No new lines could be derived, even from IVF-discarded embryonic tissues. Laboratories working on ES cells faced stringent oversight and cuts in funding. In 2006 and 2007, Bush repeatedly vetoed federal funding for the establishment of new cell lines. Advocates of stem cell research, including patients with degenerative diseases and neurological impairments, thronged the streets of Washington, threatening to sue federal agencies responsible for the ban. Bush countered these requests by holding press conferences flanked by children produced by the implantation of “discarded” IVF embryos that had been brought to life via surrogate mothers.
The ban on federal funding for new ES cells froze the ambitions of human genomic engineers, at least temporarily. But it could not stop the advance of the second step required to create permanent heritable changes in the human genome: a reliable, efficient method to introduce intentional changes in the genomes of ES cells that were already in existence.
At first, this too seemed like an insurmountable technological challenge. Virtually every technique to alter the human genome was crude and inefficient. Scientists could expose stem cells to radiation to mutate genes—but these mutations were sprinkled randomly throughout the genome, defying any attempt to directionally influence the mutation. Viruses carrying known genetic changes could insert their genes into the genome, but the site of insertion was typically random, and the inserted gene was often silenced. In the 1980s, another method to introduce a directional change in the genome—flooding cells with pieces of foreign DNA carrying a mutated gene—was invented. The foreign DNA was inserted directly into a cell’s genetic material, or its message was copied into the genome. But although the process worked, it was notoriously inefficient and prone to errors. Reliable, efficient, intentional change—the deliberate alteration of specific genes in a specified manner—seemed impossible.
In the spring of 2011, a researcher named Jennifer Doudna was approached by a bacteriologist, Emmanuelle Charpentier, about a conundrum that seemed, at first, to have little relevance to human genes or genomic engineering. Charpentier and Doudna were both attending a microbiology conference in Puerto Rico. As they walked through the alleyways of Old San Juan, past the fuschia-and-ochre houses with arched doorways and painted façades, Charpentier told Doudna of her interest in bacterial immune systems—the mechanisms by which bacteria defend themselves against viruses. The war between viruses and bacteria has gone on for so long, and with such ferocity, that like ancient, conjoined enemies, each has become defined by the other: their mutual animosity has been imprinted in their genes. Viruses have evolved genetic mechanisms to invade and kill bacteria. And bacteria have counter-evolved genes to fight back. “A viral infection [is a] ticking time bomb,” Doudna knew. “A bacterium has only a few minutes to diffuse the bomb—before it gets destroyed itself.”
In the mid-2000s, a pair of French scientists named Philippe Horvath and Rodolphe Barrangou stumbled on one such mechanism of bacterial self-defense. Horvath and Barrangou, both employees of the Danish food company Danisco, were working on cheese-producing and yogurt-making bacteria. Some of these bacterial species, they found, had evolved a